key: cord-0798566-4cksswmx authors: Higgins, Stephen T.; Klemperer, Elias M.; Coleman, Sulamunn R.M. title: Looking to the empirical literature on the potential for financial incentives to enhance adherence with COVID-19 vaccination date: 2021-01-08 journal: Prev Med DOI: 10.1016/j.ypmed.2021.106421 sha: a1c50a31fbe0be4a119aff7eb7fd2e894792f3a8 doc_id: 798566 cord_uid: 4cksswmx COVID-19 vaccination efforts are underway offering hope for saving lives and eliminating the pandemic. The most promising vaccines require two injections separated 3-4 weeks apart. To achieve heard immunity, 60-80% of the population or perhaps more must be inoculated. Anticipation of adherence challenges has generated commentaries on strategies to enhance adherence including financial incentives. A notable gap in these commentaries is any discussion of the scientific evidence regarding the efficacy of financial incentives for increasing vaccine adherence. This commentary addresses that gap. There is a body of controlled trials on incentivizing vaccine adherence, mostly to the hepatitis B virus (HBV) vaccine among injection drug users (IDUs). Prevalence of HBV infection is increasing as part of the opioid addiction crisis. The HBV vaccine entails a three-dose regimen (typically 0, 1, and 6 months) which has created adherence challenges among IDUs. Systematic literature reviews document significant benefit of financial incentives. For example, a 2019 meta-analysis (Tressler & Bhandari, 2019) examined 11 controlled trials examining HBV-vaccine adherence strategies, including financial incentives, accelerated dosing schedules, and case-management/enhanced services. Financial incentives were most effective resulting in a 7-fold increase in adherence to the vaccination regimen relative to no financial incentives (OR, 7.01; 95% CI, 2.88-17.06). Additional reviews provide further support for the efficacy of financial incentives for promoting adherence with vaccination (HBV & influenza). Overall, this literature suggests that financial incentives could be helpful in promoting the high levels of adherence to COVID-19 vaccines that experts project will be necessary for herd immunity. COVID-19 vaccination efforts are underway in the U.S. and globally, offering hope for saving lives and eventually eliminating this devastating pandemic. The most promising vaccines, including two approved for use in the U.S. (PfizerBioNTech and Moderna), require two injections separated 3-4 weeks apart. Additionally, to achieve heard immunity, infectious disease policy experts estimate that between 70-90% of the population will need to be inoculated (McNeil, 2020 , https://www.nytimes.com/2020/12/24/health/herd-immunity-covidcoronavirus.html). Those two features of this effort, vaccines requiring multiple injections separated in time and the need for adherence in the vast majority of the population, are likely to result in substantive adherence challenges especially among segments of the population who are already disproportionately burdened by the pandemic (e.g., socioeconomically disadvantaged populations, those with co-morbid conditions). This scenario has generated commentaries on the need for explicit efforts to enhance adherence including the potential need for financial incentives. For example, U.S. Presidential candidates John Delaney and Andrew Yang have recommended offering a $1,500 stimulus check for being vaccinated while economists Robert Litan and N. Gregory Mankiw have opined that an incentive of at least $1,000 would be necessary (Zeballos-Roig, 2020, https://www.businessinsider.com/covid-19-vaccine-payment-economists-stimulus-recoverycoronavirus-aid-2020-11). As another example, behavioral economists George Loewenstein and Cynthia Cryder (2020) acknowledged the need for incentives, recommending naturalistic incentives such as making air travel or access to large public events contingent on evidence of being vaccinated but expressed concerns that financial incentives could perversely undermine motivation to get vaccinated among the more altruistically inclined or exacerbate suspicion regarding the risk of vaccination among those who are already skeptical about vaccines. Individuals addicted to illicit drugs such as cocaine and heroin are a group often faced with a range of barriers including co-morbid medical conditions and socioeconomic instability that can make adherence to preventive medical regimens highly challenging. Yet that is the group in which there is the greatest amount of sound scientific evidence that modest financial incentives can indeed enhance vaccine adherence. The U.S. opioid crisis and associated increases in injection drug use (IDU) has resulted in a rise in acute hepatitis B viral (HBV) infection, a potentially fatal condition should infection become chronic. An efficacious vaccine for HBV infection is available but entails a three-dose regimen (typically 0, 1, and 6 months). Because of the substantive challenges of gaining adherence in the IDU population, a series of strategies to enhance completion of the dosing regimen have been investigated in controlled trials. A 2019 systematic review and meta-analysis of that literature (Tressler & Bhandari, 2019) examined 11 controlled trials examining adherence strategies, including modest financial incentives (mean maximal total earnings: $136 (range=44-120), accelerated dosing schedules, and case-management/enhanced services. Financial incentives were most effective resulting in a 7-fold increase in adherence (OR, 7.01; 95% CI, 2.88-17.06). Accelerated dosing schedules were also effective resulting in almost a 2-fold increase (OR, 1.90; 95% CI, 1.14-3.14), while case-management/enhanced services failed to significantly increase adherence (OR, 2.92; 95% CI, 0.54-15.66) (Figure) . Two additional systematic reviews also support the efficacy of modest financial incentives for promoting adherence with vaccination (HBV & influenza) as well as J o u r n a l P r e -p r o o f Journal Pre-proof tuberculosis screening which of course is not vaccination but also entails a multiple-visit regimen often directed at IDU users and other socioeconomically unstable or disadvantaged populations (Giles et al., 2014; Herrmann et al., 2017) . Importantly, the efficacy of modest financial incentives for improving vaccine adherence described above is consistent with a considerably larger body of evidence supporting their efficacy in promoting abstinence from addictive drug use (Davis et al., 2016) and weight loss (Pope et al., 2018) . Indeed, the amount of evidence from controlled studies supporting their efficacy for increasing abstinence from drug use or improvements in other therapeutic targets among those with addictions is striking. The Davis et al. (2016) review was the third in a systematic series on this topic that cumulatively examined 176 controlled studies published in peer-reviewed journals between 1991 through 2014 of which 151 (86%) reported statistically significant improvements in the target behavior. By any standard with which we are familiar, that is a substantial degree of empirical support for efficacy. While the literature on controlled studies examining the efficacy of financial incentives for promoting weight loss is not as large, it too is extensive dating back to the 1970s and consistently positive (Jeffery, 2012; Pope et al., 2017) . Indeed, it is safe to say that there is a general consensus among experts in both research areas that incentives work while available. Where questions arise is regarding the sustainability of therapeutic gains once the incentives are discontinued. Of course, that concern regarding relapse is largely if not exclusively obviated when used to promote vaccine adherence. We know of no evidence that the use of financial incentives in these applications has perverse or unintended adverse consequences. Overall, we believe the scientific literature strongly supports consideration of financial incentives as an evidence-based strategy for enhancing adherence to COVID-19 vaccines should J o u r n a l P r e -p r o o f Journal Pre-proof the much-anticipated adherence challenges indeed arise. Financial incentives, perhaps targeted at disadvantaged populations, in combination with the type of naturalistic incentives discussed by Loewenstein and Crowder (2020) , may be a prudent course to take. Importantly, there is sound empirical evidence demonstrating that the effect size of financial incentives increases as a positive function of the amount offered and decreases as a function of temporal delays in providing the incentives upon task completion (Lussier et al., 2006) . Thus, the magnitude and immediacy of incentives is worth keeping in mind as the challenge of gaining sufficient adherence to achieve herd immunity plays out. Determining the optimal incentive value necessary to achieve sufficient vaccine adherence is an empirical question best answered by experimental investigation of incentivizing COVID-19 vaccines. The extant literature would suggest that the $1,000-$1,500 incentives proposed by Delaney, Yang, and others would likely be highly effective, but also perhaps unnecessarily excessive. The modest values used in the HBV trials discussed above offer an evidence-based starting point but are perhaps too modest considering the importance to population health of gaining high levels of adherence in this instance. If forced to estimate based on the literature, we would anticipate that incentives in the range of $300 across both injections delivered with minimal delay (i.e., delivered by the pharmacy immediately following injection) would promote high levels of adherence, perhaps offering $100 for the first injection and $200 for the second if completed within the recommended time frame would be a good starting place (Roll & Higgins, 2000) . For example, The authors have no conflicts of interest to declare. A review of the literature on contingency management in the treatment of substance use disorders The effectiveness of financial incentives for health behaviour change: systematic review and metaanalysis Contingency management interventions for HIV, tuberculosis, and hepatitis control among individuals with substance use disorders: a systematized review Financial incentives and weight control Why paying people to be vaccinated could backfire A meta-analysis of voucher-based therapy for substance use disorders How much herd immunity is enough? NYTimes Behavioral economics and obesity Eating Disorders and Obesity: A Comprehensive Handbook 3 rd Edition The brief abstinence test: voucher-based reinforcement of cocaine abstinence A within-subject comparison of three different schedules of reinforcement of drug abstinence using cigarette smoking as an exemplar Vaccination in people who inject drugs: a systematic review and meta-analysis Top economists and 2 former 2020 presidential candidates are backing a 'vaccine stimulus' that would pay people at least $1,000 to get Covid-19 shots